Immunoglobulin-E/dinitrophenyl complexes induce nitric oxide synthesis in rat peritoneal macrophages by a mechanism involving CD23 and NF-kappa B activation.
The production of nitric oxide (NO) by rat adherent peritoneal cells stimulated with preformed IgE/Dinitrophenyl-BSA (DNP-BSA) complexes and its dependence on the activation of the transcription factor NF-kappa B were studied. Stimulation with IgE/DNP-BSA complexes at equivalence induced both the production of NO and an increased expression of the inducible isoform of NO synthase (iNOS) protein. Both events were also elicited by a rabbit polyclonal F(ab')2 anti-CD23 cross-reacting with rat CD23, thus suggesting Fc epsilon RII/CD23 antigen as the IgE-binding structure involved in the triggering of the response and ruling out an interaction of the antibody via its Fc portion. Inhibition of redox-sensitive signaling mechanisms by the antioxidant pyrrolidine dithiocarbamate (PDTC) blocked NO production, iNOS expression, and NF-kappa B activation elicited by both IgE/DNP-BSA complexes and anti-CD23 F(ab')2, thus suggesting the involvement of NF-kappa B in the signaling pathway leading to the transcriptional activation of iNOS. These results show the existence in rat peritoneal macrophages of a signaling pathway triggered by CD23 engagement that promotes nuclear translocation of NF-kappa B and transcriptional activation of the inducible isoform of NO synthase.
Bayón
Y
Y
Instituto de Biología y Genética Molecular, CSIC, Facultad de Medicina, Valladolid, Spain.
Alonso
A
A
Sánchez Crespo
M
M
D000818:Animals; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000032:analysis; D004789:Enzyme Activation; D004790:Enzyme Induction / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D012709:Serum Albumin / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013859:Thiocarbamates / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D015533:Transcriptional Activation / Q000235:genetics*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D000975:Antioxidants; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007140:Immunoglobulin Fab Fragments; D016328:NF-kappa B; D009573:Nitrites; D009687:Nuclear Proteins; D017455:Receptors, IgE; D015842:Serine Proteinase Inhibitors; D012709:Serum Albumin; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007073:Immunoglobulin E; D014108:Tosylphenylalanyl Chloromethyl Ketone; D011392:Proline; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat